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Socioeconomic inequalities in non-communicable ailments along with their risks: a summary of organized critiques.
e US.DNA damage response (DDR) and repair pathways determine neoplastic cell transformation and therapeutic responses, as well as the aging process. Altered DDR functioning results in accumulation of unrepaired DNA damage, increased frequency of tumorigenic mutations, and premature aging. Recent evidence suggests that polypeptide hormones play a role in modulating DDR and DNA damage repair, while DNA damage accumulation may also affect hormonal status. We review the available reports elucidating involvement of IGF1, GH, αMSH, and GnRH/gonadotrophins in DDR and DNA repair as well as the current understanding of pathways enabling these actions. We discuss effects of DNA damage pathway mutations, including Fanconi anemia, on endocrine function and consider mechanisms underlying these phenotypes. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] are selective regulators of follicle-stimulating hormone (FSH) production by pituitary gonadotrope cells. In a gonadotrope-like cell line, LβT2, activins stimulate FSH via the activin type IIA receptor (ACVR2A) and/or bone morphogenetic protein type II receptor (BMPR2). Consistent with these observations, FSH is greatly reduced, though still present, in global Acvr2a knockout mice. In contrast, FSH production is unaltered in gonadotrope-specific Bmpr2 knockout mice. In light of these results, we questioned whether an additional type II receptor might mediate the actions of activins or related TGFβ ligands in gonadotropes. We focused on the activin type IIB receptor (ACVR2B), even though it does not mediate activin actions in the gonadotrope-like cell line. Using a Cre-lox strategy, we ablated Acvr2a and/or Acvr2b in murine gonadotropes. The resulting conditional knockout (cKO) animals were compared to littermate controls. Acvr2a cKO (cKO-A) females were subfertile (~70% reduced litter size), cKO-A males were hypogonadal, and both sexes showed marked decreases in serum FSH levels compared to controls. Acvr2b cKO (cKO-B) females were subfertile (~20% reduced litter size), cKO-B males had a moderate decrease in testicular weight, but only males showed a significant decrease in serum FSH levels relative to controls. Simultaneous deletion of both Acvr2a and Acvr2b in gonadotropes led to profound hypogonadism and FSH deficiency in both sexes; females were acyclic and sterile. Collectively, these data demonstrate that ACVR2A and ACVR2B are the critical type II receptors through which activins or related TGFβ ligands induce FSH production in mice in vivo. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] thyroid disease (AITD) is one of the most frequent autoimmune disorders. However, the pathogenesis of AITD has not been fully elucidated. Recently, accumulating evidences have demonstrated that abnormal expression of non-coding RNAs (ncRNAs) is closely related to the etiopathogenesis of AITD. microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) are three major groups of ncRNAs, which attract increasing attention. Herein，we summarized our present knowledge on the role of microRNA, lncRNAs and circRNAs in AITD. This review focused on the importance of ncRNAs in development of the most prevalent AITD, such as Hashimoto's disease (HT) and Graves' diseases (GD). Altogether, the main purpose of this review is to provide new insights in the pathogenesis of AITD and the possibility to develop novel potential therapeutic targets. © Endocrine Society 2020. GSK1904529A All rights reserved. For permissions, please e-mail [email protected] drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of miRNAs in regulating drug resistance and leukemic stem cell (LSCs) fate, we performed global transcriptome profiling in treatment-naïve chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor; its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in pre-clinical xenotransplantation models. Integrative analysis with mRNA profiles uncovered PAK6 as a crucial target of miR-185 and pharmacological inhibition of PAK6 perturbed the RAS/MAPK pathway and mitochondrial activity, sensitizing therapy-resistant cells to TKIs. Thus, miR-185 presents as a potential predictive biomarker, and dual targeting of miR-185-mediated PAK6 activity and BCR-ABL may provide a valuable strategy for overcoming drug resistance in patients. Copyright © 2020 American Society of Hematology.In a common garden study in Maine from 2012 to 2015, we used two bee species (Apis mellifera L. and Bombus ternarius Say (1837)) and three field-recognizable bee categories ('Most Bombus', 'Halictidae', and 'Other Bees') plus an 'All Bees' data aggregation to compare 17 native and 68 introduced plant taxa. Data were from three 1-min timed periods per flowering plant taxon on a given day at a site. We observed 17,792 bees and found that their response varied by bee species or group. Using mixed models to analyze our data, we found that native bees had higher visitation rates on native plants, while A. mellifera visited both native and introduced plants. Most groups visited native late-flowering and native mid-late-flowering plants at higher rates. 'All Bees' were attracted to native perennials (vs annuals and shrubs) and to tall plants, both native and introduced; A. mellifera was attracted to introduced perennials, to introduced tall plants, and to lower-growing native plants. Asclepias tuberosa L. elicited a strong response from B. ternarius. In only two of six pairs of wild types and cultivars, bees visited wild types more. Plants with long bloom periods and with small, densely arranged white flowers attracted higher bee visitation than did other configurations (e.g., Origanum vulgare L., one of our most attractive taxa). A general linear model showed that linear combinations of flower density, floral resource height, flower corolla depth, and flowering duration explained significant variation in visitation rates for each of the different bee taxa groups. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail [email protected].
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